This proposal is for a competitive renewal of a K24 Award from the NIDA. K24 support has been pivotal in Dr. Moore developing a program of patient-oriented research and training focused on HIV-infected patients with a history of drug abuse. The core of his program is a longitudinal cohort of HIV-infected patients receiving care. Injecting drug use (IDU) is the risk factor for HIV transmission in over half of the cohort, and active drug use is common. In the past 5 years, Dr. Moore and investigators he mentors have shown that IDU is associated with significant lower rates of HIV viral suppression, immunologic response, and an increase by 50% in the relative incidence of AIDS-defining illness in IDUs compared to non-IDUs. Active drug use is a particular barrier to HIV response, yet even short-term abstinence is associated with a significant improvement in outcomes. A relative decline in the benefit of HAART in drug users has important implications for the management of HIV infection since IDU transmission accounts for about 25% of HIV cases in the U.S., and 3-4 million HIV-infected persons worldwide. The cohort now has over 21,000 person-years of follow-up time; The proposed research will focus on long-term treatment and outcomes of HIV-infection in IDUs, and on co-morbidity such as hepatitis C. In addition, new collaborative efforts will provide new resources for research and mentoring. These include a new HIV primary care clinic on-site within a substance abuse treatment facility where intervention strategies to improve care and outcomes are being assessed; A longitudinal cohort from a multisite U.S. network of HIV providers will provide opportunities to assess the generalizability of our findings and expand the scope of our research; and a collaboration with the AIDS Link to lntravenous Experiences (ALIVE) cohort that will provide comparisons to HIV-infected drugs users who are not in care and HIV seronegative drug users. Renewal of the K24 Award will support continued research productivity and mentoring to improve care of the HIV-infected IDU.